Sympathetic Activation in Congestive Heart Failure: Evidence, Consequences and Therapeutic Implications

Congestive heart failure (CHF) is characterized not only by profound abnormalities in the haemodynamic profile but also by changes in sympathetic cardiovascular function. These neurogenic abnormalities are important features of the disease that can affect the prognosis of CHF and to become a target for therapeutic intervention. This article addresses 4 major issues. It will first examine the evidence that a hyperadrenergic state is a hallmark of CHF, based on data collected via indirect (plasma norepinephrine, power spectral analysis of the heart rate signal) and direct (microneurography, norepinephrine spillover, radioimaging techniques visualizing myocardial neural network) approaches. It will then provide an overview on the central, reflex and metabolic factors potentially responsible for the phenomenon. The review also analyses the clinical consequences of the adrenergic alteration, with particular emphasis on the effects of the sympathetic overdrive on disease progression, arrhythmogenic threshold, adverse clinical outcomes as well as sudden death. The final part of the review will examine the therapeutic implications of the above mentioned findings and discuss the effects of pharmacological and non- pharmacological interventions on the sympathetic abnormalities of the heart failure state.